HU204490B - Process for selective reduction of nitril-group - Google Patents

Abstract

Redn. is carried out in a polar solvent, in the presence of Raney nickel catalyst, acid and a sulphur comprising cpd., under hydrogen, at 10-60 deg.C and 1-5 bar pressure. The completion of redn. is indicated by redn. of H2 consumption. The ratio of the catalyst and the sulphur cpd. to the nitrile content is 5-15w/w% and 0.01-5w/w% respectively.

Description

The present invention relates to a process for converting a nitrile group of an organic compound into an aldehyde group by hydrogenation using Raney nickel catalyst in a polar solvent in the presence of an acid.

According to the literature, Raney nickel reduction of nitriles can give rise to primary, secondary or tertiary amines, aldehydes, alcohols, alkanes and N-heterocyclic compounds (Houben-Weil, Methoden Der Organischen Oiemie, IV / 1, Reduction I, 111, Verlag, Stuttgart). , New York, 1980). The formation of aldehyde is promoted when an amine-type aldehyde reagent is added to the reaction mixture and the resulting aldehyde derivative is no longer or only very slowly reduced. Examples of such reagents are phenylhydrazine and its substituted derivatives (Compt. Ed., 252, 1339 (1961), and 253, 134 (1961)), semicarbazide (U.S. Patent 957,029 (1958), Angew. Chem., 67,156 (1957)), 1,2-dianilinoethane (Chem. Ber. 90, 617 (1957)). The disadvantages of these methods are that the use of organic excipients complicates the process and the release of the aldehyde from its derivative causes further losses.

Conversion of nitriles to aldehyde can be accomplished in 70-85% yield, depending on the molecular structure, of a 1: 1: 2 mixture of acetic acid pyridine with 30-40% by weight of Raney nickel catalyst and 200% by weight of sodium hypophosphite, 40-45 ° C [J.Chem. Soc., 3961 (1962)]. The disadvantage of this process is that large amounts of phosphorus-containing wastewater would be produced.

No. 17,767 (1971). According to the Japanese patent, some organic nityl can be converted to quantitative aldehyde at room temperature with Raney nickel catalyst in a solvent mixture of water-acetic acid-pyridine in the presence of Snd ₄ . In our experience, the process is not reproducible: SnCl _{4 is} hydrolyzed in the specified solvent mixture and the catalyst is deactivated.

No. 43,057 (1966). According to the GDR patent, cyanopyridines can be converted into nicotinaldehydes in Raney nickel in the presence of CO ₂ in an aqueous medium. The disadvantage of the process is that the reaction is quite slow: for example, 3-danopyridine can be converted to nicotinaldehyde in only 8 hours at a total pressure of 20 bar in a yield of 72%.

Certain nitriles 65-70% yield of the corresponding aldehydes can be hydrogenated with Pd (OH) ₂ / _BaSO4 catalysts tor ^2, 0.5 M hydrochloric acid [Liebigs Annalen Chemie hoarfrost, 600.115, 126 (1956); Angew. Chem., 69, 60 (1957)], but experience has shown that for many nitriles the yield is very low, below 10%.

Conversion of nitriles to aldehydes can be accomplished with E Raney nickel catalyst or with undissolved Raney alloy in formic acid without hydrogen [J. Chem. Soc., 5880 (1964); J. Chem. Soc., 5775 (1965); 159,899 (1971). s. Hungarian patent]. £

The efficiency of conversion to the aldehyde is generally above 40%, depending on the reaction conditions and the structure of the molecule. The disadvantage of the process is that a large amount of Raney nickel or Raney alloy, 100-150% by weight, is required for the complete conversion. 6

Raney nickel hydrogenation of nitriles can be carried out at room temperature, at atmospheric pressure, in tetrahydrofuran-water, in the presence of a molar amount of sulfuric acid. [Angew. Chem., 80, 152- (1968); Chem. Bér., 102, 2770 (1969); Arch. Pharm., 309, 166 (1976). The reaction time is from 2 to 15 hours, depending on the structure of the organic nitrile, using Raney nickel at 20-30% by weight, starting with 0.1 mole of nylryl. Disadvantages of the procedure:

a) the catalyst gradually dissolves / deactivates in the reaction mixture and therefore the catalyst / nitrile ratio must be increased to increase the size;

b) many nitriles can be converted to the corresponding aldehyde in only moderate yields of 50-60%;

»C) the reduction does not stop after the formation of the aldehyde, but alcohol and then hydrocarbon are formed, which makes the operation difficult.

The present invention is based on the discovery that these disadvantages can be overcome by hydrogenation of the nitrile group of the organic compounds to the aldehyde group in the presence of Raney nickel catalysts, in a polar solvent, an acid and a sulfur-containing compound. After complete conversion of the nitrile group, the hydrogen uptake stops or the rate of hydrogen uptake drops to 1-10% of the previous value because the reduction of aldehyde under these conditions is inhibited, so that the yield from the corresponding nitrile is very good, often close to quantitative.

The process of the present invention comprises hydrogenating the nitrile-containing organic compound in a polar solvent with Raney nickel catalyst in the presence of an acid and a sulfur-containing compound until the nitrile group is completely reacted, and then separating the catalyst in a known manner. The temperature of the reaction mixture during hydrogenation is 0-120 ° C, preferably 10-60 ° C, and the pressure is 0.5-20 bar, preferably 1-5 bar.

Polar solvents include alcohols (e.g. methanol, ethanol, 2-propanol, benzyl alcohol) or alcohol and other polar solvents or solvents (e.g., water, acetic acid, pyridine, ethyl acetate, dioxane, dimethylformamide, butyl acelate tetrahydro). furan, diethyl ether) may be used.

The acid may be inorganic (e.g. hydrochloric acid, sulfuric acid) or organic acids (e.g. acetic acid, p-toluenesulfonic acid) in an amount of 0.5 to 10 molar equivalents relative to nitrile, preferably 0.8 to 2 molar equivalents.

The amount of Raney nickel catalyst is 150 wt%, preferably 5 to 15 wt%, based on the organic compound containing the nylryl group.

A sulfur-containing compound that increases the selectivity of the reduction may be inorganic [e.g. K ₂ S, Na ₂ S, (NH ₄ ) ₂ S, Na ₂ S ₂ O ₅ , NaHSO ₃ , Na ₂ SO ₃ , Na ₂ S ₂ O ₄ ] or organic (e.g. dimethylsulfide, diethylsulfide, dimethyl sulfoxide, thiophenol, thiourea, thiophene, diphenyl sulfide, diphenyl disulfide, diethyl disulfide). The amount of the sulfur-containing compound is preferably not more than 10% by weight, preferably 0.01 to 5% by weight, relative to the nitrile.

In our experience, the same good results can be obtained either by adding the sulfur-containing compound to the reaction mixture before hydrogenation or by dissolving it separately in the catalyst in a polar solvent, followed by mixing.

After 204 490 Β, the suspension is added to the reaction mixture, with or without decantation. The Raney nickel catalyst can be added to the reaction mixture directly, wet or rinsed with a polar solvent for hydrogenation prior to use. as above with a polar solvent containing a sulfur-containing compound.

The main advantages of the process according to the invention are:

- after complete conversion of the nitrile group, the hydrogen uptake stops or drops to 1-10% of the former value, so that the production from the corresponding aldehyde is very good on a commercial scale, often close to quantitative;

- the dissolution-deactivation of the Raney nickel catalyst is negligible even in the presence of mineral acid, so that the reaction is rapid (1-5 hours) even at less than 10% by weight relative to nitrile;

- the Raney nickel catalyst is non-pyrophoric due to the adsorption of the sulfur compound and its filtration is harmless at the end of the reaction;

the reduction can be performed in a standard apparatus.

The following examples illustrate the process of the invention without limiting it. (The percentages in the examples refer to the starting nitrile.)

In the examples, t% refers to weight%

Example 1 120 g (0.62 mol) of 3,4,5-trimethoxybenzonitrile, 550 cm ^{3 of} methanol, 36 cm ³ (0.66 mol) of 98% sulfuric acid (with stirring and cooling) were charged into a dm ³ autoclave. ), 4.5 cm ³ (4.1% by weight) of dimethyl sulfoxide and 10 g (8.3% by weight of Raney nickel) after purging with nitrogen followed by hydrogen with vigorous stirring (n = 700-800 min ' ¹ ), carrying out the reduction in the hydrogen consumption ceases during approx. 4 hours at 20-25 ° C and 4-7 bar pressure. After filtration, an aqueous hydrochloric acid ³ 90 5% was added and the methanol was distilled off and the remaining aqueous The suspension was stirred with 200 cm ^{3 of} water at 5-10 ° C, then filtered and washed with 2 x 100 cm ^{3 of} water. The yield of 3,4,5-trimethoxybenzaldehyde was 119 g (97.6%).

Example 2

All were prepared as in Example 1, but instead of 3,4,5-trimethoxybenzonitrile, 150 g (0.62 mole) of 3,5-dimethoxy-4-bromobenzonitrile was added. The yield of 3,5-dimethoxy-4-bromobenzaldehyde was 137 g (90.2%).

Example 3

A 200 cm ³ hydrogenation flask was charged with 10.3 g (0.1 mol) of benzonitrile, 10 cm ^{3 of} methanol, 40 cm ^{3 of} n-butyl alcohol and 6.5 cm ³ (0.12 mol) of 98% sulfuric acid was suspended 11 mg (0.11 wt%) of Na ₂ S. 9H ₂ O10 cm ³ of water, was prepared and, after decanting the suspension 20 cm ³ catalyst was rinsed with methanol for 5 min 1.5 g (15%) of Raney nickel hydrogenation flask.

After purging with nitrogen and then with hydrogen, the reduction was continued with stirring at 40-45 ° C and 1 bar until the rate of hydrogen depletion decreased to 5-6% of the former value. After filtration of the catalyst, the aliquot of the mixture was determined by precipitation with 2,4-dinitrophenylhydrazine (A. Vogel, Textbook of Practical Organic Chemistry, 3rd ed., Longraans, London, 1954), yielding 10.4 g of benzaldehyde. g (98.1%).

Example 4

200cm ³ inch hydrogenation flask was added (78 mmol) of o-toluolnitrilt 9.1 g, 70 cm ³ of ethanol, 20 cm ³ (350 mmol) of acetic acid, 0.45 g of 4 cm ³ / dm ³ methanol solution of thiourea (0, 02% by weight) and 1.2 g (13% by weight) of Raney nickel Following the procedure of Example 3, the yield of 2-methylbenzaldehyde was 9.0 g (96.4%).

Example 5

Each was prepared as in Example 3 but using 9.9 g (0.1 mol) of β-ethoxypropionitrile instead of benzonitrile. The yield of β-ethoxypropionaldehyde was 8.4 g (82.4%).

Example 6

15 g (0.28 mol) of acrylonitrile, 200 cm ^{3 of} methanol, 16 cm ³ (0.29 mol) of 96% sulfuric acid in 0.3 cm ³ (2.2 wt%) were weighed into a 0.5 dm ³ autoclave. dimethylsulfoxide and 2 g (13%) of Raney Nickel, after purging with Nitrogen followed by Hydrogen at 25 ° C and 2 to 5 bar, are stirred until hydrogen consumption ceases (about 1 hour). After working up the product as in Example 3, the yield of propionaldehyde was 14.1 g (85.9%).

Example 7

By performing the experiment as in Example 6 but using other nitriles instead of acrylonitrile, the following results were obtained:

Nitrile (g) aldehyde Production% propionitrile (15) propionaldehyde 86.1 benzonitrile (28) benzaldehyde 94.0 3-Methoxybenzonitrile (30) 3-methoxy-benzal- dehydrated 94.5 4-Methyl-beuzonitrile (35) 4-methyl-benzalde- bridge 96.8 3-Methoxy-4-bromobenzonitrile (45) 3-methoxy-4- bromo-benzalde- bridge 90.1 4-tert-butyl-benzonitrile (40) 4-tert-butyl benzaldehyde 93.5 lauryl nitrile (40) lauric aldehyde 81.5

3-hydroxybenzonitrile (35) 3-hydroxybenzonitrile

dehydrated 85.4 α-Phenylbutyric acid nitrile (35) the phenyl butiralde- 6-methoxy-3-cyano-quinoline bridge 71.5 (45) 6-methoxy-3-for mil-quinoline 81.0 caproic acid nitrile (20) kapronaldehid 84.1 benzyl cyanide (33) 3,4-dimethoxybenzyl cyanide phenylacetaldehyde 89.2 nid (50) 3,4-dimethoxy-Fe phenyl acetaldehyde 82.6

HU 204 490 Β

Nitrile (g)

Aldehyde Running%

3,4-Dichlorobenzonitrile (50) 3,4-Dichlorobenzonitrile

aldehyde 92.5 p-phenoxybenzonitrile (50) p-phenoxy-benzal- Dehli 91.0 L-gluconic acid nitrile (21) L-glflkőz 75.3 2-Naphtonitrile (35) 2-naphthaldehyde 91.5

Example 8

In the same manner as in Example 6, but using sulfuric acid instead of 80 cm ³ (1.4 mol) of acetic acid in methanol, a mixture of 30 cm ^{3 of} pyridine and 50 cm ^{3 of} water, the propionaldehyde yield was 13.0 g (79.2%). ). 15

Example 9

The experiment was carried out as in Example 6, but using 30 mg (0.2% by weight) of diphenyl disulfide instead of dimethylsulfoxide and producing 12-16 bar of apropionic aldehyde instead of 3-5 bar, yielding 13.8 g of 84 , 1%).

Example 10

The experiment was carried out as in Example 6, but using 25 mg of Na ₂ S ₂ O ₅ instead of dimethyl sulfoxide by stirring with 20 cm ^{3 of} methanol and 0.8 g (5.3 wt.%) Of Raney nickel for 5 minutes. and then, after decantation, washed into the autoclave with a portion of the methanol solvent. The yield of propionaldehyde was 13.9 g (84.7%). 30

Example 11

The experiment was carried out as in Example 1, but the temperature during the reduction was 50-55 ° C instead of 20-25 ° C. The yield of 3,4,5-trimethoxybenzaldehyde was 35,118 g (96.8%).

Example 12

All proceed as in Example 3, but using 15 µl (0.12% w / w) of diethylsulfide 40 instead of Na ₂ S. 9H ₂ O. The yield of benzaldehyde was 10.2 g (96.2%).

Example 13

All proceed as in Example 1, but using 0.1 g (0.08% by weight) of diethyl disulfide instead of dimethyl sulfoxide. The yield of 3,4,5-trimethoxybenzaldehyde was 117 g (96.0%).

Example 14 50

Each was prepared in the same manner as in Example 1, but instead of 3,4,5-trimethoxybenzonitrile 80 g (0.6 mol) phenylglycolic acid nitrile and methanol: propanol: dioxane = 10: 9: 2, 420 A total volume of cm ^{3 was} used. The phenyl glycol aldehyde yield was 64.1 g 55 (78.3%).

Example 15

All of the procedures of Example 1 were followed, but the temperature during the reduction was not 20-25 ° C but 5-10 60 ° C and the pressure was not 4-6 bar but 8-10 bar. The yield of 3,4,5-trimethoxybenzaldehyde was 118 g (96.8%).

Example 16 dm ³ autoclave was charged with 85 g (0.72 mol) of 4-methyl-benzonitrile, 300 cm ³ of methanol, 120 g (0.7 mol) of p-toluene sulfonic acid, 200 cm ^3, 0.05 cm vizef ³ (0.05% by weight) of isobutyl alcohol (5 cm ^{3 in} methanol solution) and 15 g (18% by weight) of Raney nickel after purging with Nitrogen followed by Hydrogen were stirred at 60-65 ° C and 46 bar. reduction until hydrogen consumption ceases. After cooling and filtration, the amount of 4-methylbenzaldehyde (78.1 g) and the yield (89.5%) were determined from the filtrate by gas chromatography.

Example 17 52.8 g (0.4 mole) of phenylpropionitrile, 300 cm ^{3 of} ethanol, 25 cm ^{3 of} tetrahydrofuran 22 cm ^{3 of} 96% sulfuric acid (0.4 mole) were charged into a dm ³ autoclave. , 05 cm ³ (0.08% by weight) of dimethyl sulfide and 5 g (9.5% by weight) of Raney nickel L after purging with nitrogen followed by hydrogen with stirring at 15-20 ° C and a pressure of 2-4 bar. the reduction is carried out until the hydrogen consumption ceases. After filtration, the filtrate was used to determine the phenylpropionaldehyde yield (85.5%) by gas chromatography.

Claims (7)

PATENT CLAIMS A process for converting a nitrile group of an organic compound to an aldehyde group by hydrogenation with Raney nickel catalyst in a polar solvent in the presence of an acid, characterized in that the hydrogenation preferably contains up to 10% by weight, preferably 0.01 to 5% by weight, of sulfur. and after the complete reduction of the nitrile, the catalyst is separated off in a known manner. The process according to claim 1, wherein the sulfur-containing compound is an inorganic compound, Na ₂ S, (NH ₄ ) ₂ S, Na ₂ S ₂ O ₄ , Na ₂ S ₂ O ₅ -of or an organic compound such as diethylsulfido-thiobutyl alcohol, dimethylsulfoxide, thiophene-thiophenol, diphenyl disulfide, thiourea. Process according to claim 1 or 2, characterized in that the Raney nickel is present in an amount of 1 to 50% by weight, preferably 5 to 15% by weight, based on the nihil. 4. Process according to any one of claims 1 to 3, characterized in that the acid is inorganic acids, hydrochloric acid, sulfuric acid or organic acids, acetic acid, p-toluenesulfonic acid. 5. Process according to any one of claims 1 to 3, characterized in that the amount of acid is 0.5 to 10 molar equivalents, preferably 0.82 molar equivalent, relative to nihil. 6. Process according to any one of claims 1 to 3, characterized in that the hydrogenation is carried out at a temperature of 0 to 120 ° C, preferably at a temperature of 10 to 60 ° C. 7. Process according to any one of claims 1 to 4, characterized in that the hydrogenation is carried out at a pressure of 0.5 to 20 bar, preferably at 1 to 5 bar.